Field of the Art
The present invention relates to devices and methods for cold plasma medical treatment, and, more particularly, to such devices and methods for cold plasma electroporation of medications and bioactive agents into cells.
Background Art
Cold plasmas (i.e., non-thermal plasmas) are produced by the delivery of pulsed high voltage signals to a suitable electrode. Cold plasma devices may take the form of a gas jet device or a dielectric barrier discharge (DBD) device.
Electroporation is the process of exposing cells to electrical fields, as illustrated in FIG. 1. When a biological cell 180 is exposed to programmed electric pulses from electrodes 170, the lipid membrane of the cell can be altered and become permeable 160. The change in the cell membrane may be of a plastic (temporary) or permanent nature, and these changes are commonly referred to as reversible or irreversible permeabilization, respectively.
One of the primary reasons to electroporate a cell, or group of cells, is to transport a molecule across the membrane that otherwise would be unable to cross this barrier, or would require cellular energy to pump/transport in the absence of applied energy. Therefore electroporation allows the cell membrane to become permeablized, and is frequently used to either insert proteins 110 into the cell membrane, introduce large 130 or small 120 molecules into the cell(s), induce cellular fusion 140, or to destroy the cell membrane 150 altogether.
Irreversible premeabilization can permanently damage a cell and lead to apoptosis or other mechanisms of cell death. Controllable apoptosis has been used in biofouling control, debacterialization, and drug-free cancer therapies.
Reversible electroporation is primarily used as a method of molecular delivery, transferring a wide array of molecules, such as drugs, ions, dyes, tracers, oligonucleotides, RNA, antibodies, proteins, etc., into and out of cells. There are several advantages to using electroporation-moderated molecular delivery over conventional methods. Electroporation is generally non-invasive, drug free, non-toxic and rapidly accomplished. Due to the fact that electroporation is a physical process between the supplied electric field and the cell membrane, it is less influenced by the specific cell type when compared to conventional methods.
Electroporation is demonstrably effective in both in vivo and in vitro clinical studies and applications, and has been employed for treating various cancers including lung, skin, breast, leukemia, specific bone cancers, and for DNA vaccination.